Inhibitors of ADP-induced platelet aggregation prevent fibrinogen binding to rabbit platelets and cause rapid deaggregation and dissociation of bound fibrinogen.
125I-fibrinogen binds to washed rabbit platelets when they ar stimulated wit ADP, and it has previously been observed that fibrinogen binding is prevented by several inhibitors of ADP-induced aggregation. We have now shown that other inhibitors of aggregation, the phosphodiesterase inhibitors caffeine and dipyridamole, and colchicine and cytochalasin B which affect the platelet cytoskeleton, also inhibit specific 125I-fibrinogen binding. A positive correlation was observed between ADP-induced aggregation and fibrinogen binding at limiting concentrations of these inhibitors. Colchicine and cytochalasin B appear to act independently, with no indication of synergism. When any of these inhibitors, as well as those previously tested (EDTA, EGTA, PGE1 and PGI2) was added to platelets that had already been stimulated with ADP and undergone considerable aggregation and fibrinogen binding, it caused rapid deaggregation of the platelets and dissociation of bound fibrinogen, although in some cases the inhibitory effects were not as pronounced as when the inhibitor was added before ADP stimulation. These observations reinforce the concept that fibrinogen plays an essential role in the formation of ADP-induced platelet aggregates.
D000244:Adenosine Diphosphate / Q000494:pharmacology*; D000818:Animals; D001665:Binding Sites; D001792:Blood Platelets / Q000378:metabolism*; D002110:Caffeine / Q000494:pharmacology; D003078:Colchicine / Q000494:pharmacology; D003571:Cytochalasin B / Q000494:pharmacology; D004176:Dipyridamole / Q000494:pharmacology; D004492:Edetic Acid / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D011464:Epoprostenol / Q000494:pharmacology; D005340:Fibrinogen / Q000378:metabolism*; D006801:Humans; D010974:Platelet Aggregation / Q000187:drug effects*; D011458:Prostaglandins E / Q000494:pharmacology; D011817:Rabbits
D011458:Prostaglandins E; D003571:Cytochalasin B; D002110:Caffeine; D004533:Egtazic Acid; D000244:Adenosine Diphosphate; D004176:Dipyridamole; D005340:Fibrinogen; D004492:Edetic Acid; D011464:Epoprostenol; D003078:Colchicine